Bacterial infections, especially bacterial infections of the respiratory tract, are a major problem for production animals such as cattle, pigs, sheep, and other livestock. Bacterial infections are also a common problem with companion animals such as cats, dogs, and horses. Bacterial infections are typically treated using antibiotics.
A class of broad spectrum antibiotics classified as D-(threo)-1-p-substituted phenyl-2-halogenoacetylamido-1,3-propanediols are known in the art. This class of antibiotics includes chloramphenicol (D-(threo)-1-p-nitrophenyl-2-dichloroacetamido-1,3-propanediol), thiamphenicol (D-(threo)-1-p-methylsulfonylphenyl-2-dichloroacetamido-1,3-propanediol), fluorthiamphenicol (D-(threo)-1-p-methylsulfonylphenyl-2-difluoroacetamido-1,3-propanediol) and tevenel (D-(threo)-1-p-aminosulfonylphenyl-2-dichloroacetamido-1,3-propanediol) (See, U.S. Pat. No. 4,235,892 to Nagabhushan). Replacing the primary hydroxyl group at C-3 of chloramphenicol by chlorine or bromine, however, destroys the biological activity thereof (F. E. Hahn, Antibiotics, Ed. Gottlieb and Shaw, Springer-Verlag, New York, (1967), p. 308; F. E. Hahn et al, Antibiotics and Chemotherapy, 6, No. 9, 531 (1956); L. Cima and A. Ilecto, Il Farmaco, Ed. Sc. 12, No. 6, 535 (1957); S. Mitsuhasi et al, Jap. J. Microbiol. 13, No. 2, 177-80 (1969); M. Kono et al, Jap. J. Microbiology 15 (3), 219-27 (1971); and U.S. Pat. No. 4,235,892 to Nagabhushan).
U.S. Pat. No. 4,235,892 to Nagabhushan discloses D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds that are allegedly useful as antibiotics. Florfenicol, [(R-(R*, S*)]-2,2-dichloro-N-[1-fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl] ethyl]acetamide or D-threo-2,2-dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-methylsulfonyl) phenyl]ethyl]-acetamide), commercially available from Schering-Plough Animal Health, New Jersey as NUFLOR®, is an example of an antibiotic in this class of compounds.
United States published patent application no. U.S. 2003/0216447 to Kohan et al. and United States published patent application no. U.S. 2003/0220302 also to Kohan et al. each disclose compositions comprising flunixin and a florfenicol or florfenicol-like compound that are allegedly useful for treating microbial infections in animals.
International publication WO 03/077828 discloses fluorfenicol-type antibiotics that allegedly exhibit antimicrobial activity.
U.S. Pat. No. 5,556,829 to Camaggi et al. discloses N-alkyl amides substituted on the alkyl group that are allegedly useful as herbicides.
U.S. Pat. No. 5,883,115 to Santus et al. discloses the transdermal delivery of the eutmer of a chiral drug when the eutomer has greater clearance and pharmacodynamic activity than a racemic mixture of the chiral drug.
Many of the known antibiotics, however, have side effects. For example, chloramphenicol is known to cause anemia. Furthermore, the known antibiotics can be ineffective in some animals, typically because they are cleared too rapidly. Additionally, some of the antibiotics are toxic to some animals. Accordingly, there is a need in the art for improved antibiotics and, in particular, new antibiotics that fall within the same general class as the D-(threo)-1-p-substituted phenyl-2-halogenoacetylamido-1,3-propanediols and the D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds.
Citation of any reference in Section 2 of this application is not to be construed that such reference is prior art to the present application.